Organophotocatalytic late-stage N-CH3 oxidation of trialkylamines with O2 in continuous flow

Mandigma, Mark John P. and Žurauskas, Jonas and MacGregor, Callum I. and Edwards, Lee J. and Shahin, Ahmed and d’Heureusea, Ludwig and Yip, Philip and Birch, David J. S. and Gruber, Thomas and Heilmann, Jörg and John, Matthew P. and Barham, Joshua P. (2021) Organophotocatalytic late-stage N-CH3 oxidation of trialkylamines with O2 in continuous flow. Preprint / Working Paper. ChemRxiv, Cambridge, UK. (https://doi.org/10.33774/chemrxiv-2021-zpfxf)

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Abstract

We report an organophotocatalytic, N-CH3-selective oxidation of trialkylamines in continuous flow. Based on the 9,10-dicyanoanthracene (DCA) core, a new catalyst (DCAS) was designed with solubilizing groups for processing in flow which allowed harnessing of O2 as a benign reagent for late-stage photocatalytic N-CH3 oxidation of natural products and active pharmaceutical ingredients. These substrates bear functional groups which are not tolerated by previous methods. The organophotocatalytic process benefited from the flow parameters, affording cleaner reactions in short residence time of 13.5 mins and productivities of up to 0.65 g / day. Mechanistic studies found that catalyst derivatization not only enhanced solubility of the new catalyst compared to DCA, it profoundly diverted the photocatalytic reaction mechanism from singlet electron transfer (SET) reductive quenching with amines to energy transfer (EnT) with O2.

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